This invention relates to new chemotherapeutic drugs for the treatment of neoplastic diseases. Successful cancer chemotherapy requires selective elimination of neoplastic cells both at the primary site and distant metastases. Most drug protocols attempt to exploit the growth characteristics of transformed cells that usually centers on loss of regulated growth. Thus, most chemotherapeutic agents selectively attack dividing cells both neoplastic and normal, and doses that are adequate to eliminate the cancerous tissues usually annihilate the host. To limit the detrimental effects of the drugs, administration of cytotoxic agents has been controlled to effect extensive destruction of the neoplastic cells while allowing the affected normal cells to recover. Oncologists, who regularly walk this tightrope, often observe that the therapy eventually fails to control the cancer. To overcome the inadequacies of standard drug therapy, efforts are made to more effectively target the drugs specifically to the cells of interest. The most general approach is to try to infuse the drugs directly into the tumor tissue so as to maintain high drug concentrations in the vicinity of tumor cells and somewhat lower concentrations elsewhere to control the detrimental effects to normal tissues. A second approach is to attempt to target the drugs directly to the tumor cells to maintain a high localized level of drug. Although considerations of this approach date back to the turn of the century when it was first suggested by Paul Ehrlich, as reported by R. Arnon and M. Sela in Immunological Rev. (1982) Vol. 62, page 5, little practical success has been achieved. The development of monoclonal antibodies in the mid-seventies reinvigorated these programs since specifically tailored antibodies could be developed in unlimited supply for use in targeting such agents which have become commonly referred to as "Magic Bullets".
Although the application of monoclonal antibodies for directing drugs and toxins to neoplastic cells was anticipated to result in major breakthroughs in cancer chemotherapy, it has produced limited success. There are many problems that this form of therapy must overcome.
The purpose of this invention is to provide novel compositions that overcome problems of the past by limiting the detrimental effects of drugs on normal cells, while destroying neoplastic cells.